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Neuroprotective roles of the P2Y2 receptor

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Abstract

Purinergic signaling plays a unique role in the brain by integrating neuronal and glial cellular circuits. The metabotropic P1 adenosine receptors and P2Y nucleotide receptors and ionotropic P2X receptors control numerous physiological functions of neuronal and glial cells and have been implicated in a wide variety of neuropathologies. Emerging research suggests that purinergic receptor interactions between cells of the central nervous system (CNS) have relevance in the prevention and attenuation of neurodegenerative diseases resulting from chronic inflammation. CNS responses to chronic inflammation are largely dependent on interactions between different cell types (i.e., neurons and glia) and activation of signaling molecules including P2X and P2Y receptors. Whereas numerous P2 receptors contribute to functions of the CNS, the P2Y2 receptor is believed to play an important role in neuroprotection under inflammatory conditions. While acute inflammation is necessary for tissue repair due to injury, chronic inflammation contributes to neurodegeneration in Alzheimer’s disease and occurs when glial cells undergo prolonged activation resulting in extended release of proinflammatory cytokines and nucleotides. This review describes cell-specific and tissue-integrated functions of P2 receptors in the CNS with an emphasis on P2Y2 receptor signaling pathways in neurons, glia, and endothelium and their role in neuroprotection.

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Acknowledgments

This work was supported by NIH grants AG018357, DE017591, and DE07389.

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Authors and Affiliations

  1. Department of Biochemistry, University of Missouri, 540E Life Sciences Center, 1201 Rollins Road, Columbia, MO, 65211-7310, USA

    Gary A. Weisman, Deepa Ajit, Lucas T. Woods, Christina Thebeau, Jean M. Camden & Laurie Erb

  2. Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO, USA

    Gary A. Weisman & Troy S. Peterson

  3. Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, USA

    Gary A. Weisman, Deepa Ajit, Troy S. Peterson, Lucas T. Woods, Christina Thebeau, Jean M. Camden & Laurie Erb

  4. Biomedical Sciences Department, Missouri State University, Springfield, MO, USA

    Richard Garrad

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Weisman, G.A., Ajit, D., Garrad, R. et al. Neuroprotective roles of the P2Y2 receptor. Purinergic Signalling 8, 559–578 (2012). https://doi.org/10.1007/s11302-012-9307-6

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